Relma-cel (JWCAR029) in relapsed and refractory B-cell non-Hodgkin lymphoma: A two-year survival update of a phase I study.

Abstract

e19555 Background: B-cell non-Hodgkin lymphoma (B-NHL) has a very poor prognosis. Relma-cel (JWCAR029) is a CD19-targeted chimeric antigen receptor T (CAR-T) cell suspension. In a phase I trial performed in November 2017 in Beijing Cancer Hospital, China, JWCAR029 was used to treat relapsed/refractory B-NHL (R/R B-NHL) in adult patients, showing a high response rate and persistent response. This report aimed to update 2-year survival data generated in the above trial. Methods: This was an open-label, dose-escalating phase I study (JWCAR029-001, NCT03344367) involving patients with R/R B-NHL. The patients received a 3-day treatment with the conditioning chemotherapy regimen, consisting of fludarabine (25 mg/m2/day) and cyclophosphamide (250 mg/m2/day). Then, they received a single dose of intravenous JWCAR029 (25×106, 50×106, 100×106, or 150×106 CAR T cells). Two-year PFS and OS after JWCAR029 treatment were evaluated. The data were updated till the cut-off date of January 18, 2021. Results: A total of 23 patients with R/R B-NHL were enrolled, of whom 22 completed single-dose JWCAR029 cell infusion. All patients completed the 2-year follow-up, with a median time of 24.2 (95%CI 24.0-24.3) months. Based on the efficacy analysis set comprising 20 patients, the best ORR and CRR were 85.00% and 70.00%, respectively. In subgroup analysis, 1-year ORR and CRR in patients administered 100×106 cells were both 3/5 (60%); they were both 5/8 (62.5%) in those administered 150×106 cells. The 1-year and 2-year PFS rates (11 patients censored) were both 55.0%. Median PFS was not reached (95%CI 3.0 months-NA). The 1-year and 2-year PFS rates in patients administered 100×106 cells were both 60.0%; these values were both 62.5% in individuals treated with 150×106 cells. The 1-year and 2-year OS rates (3 patients censored) were both 68.6%. Median OS was not reached (95%CI 10.4 months-NA). The 1-year and 2-year OS rates in patients administered 100×106 cells were both 60.0%; these values were both 75.0% in those treated with 150×106 cells. A total of 6 patients (30%) died. No grade 3 and above CRS or NT were found. Conclusions: JWCAR029 was approved in China in September 2021 after the RELIANCE study (NCT04089215) reported its excellent efficacy and tolerable toxicity in the treatment of relapsed/refractory B-cell lymphoma. This report indicated that R/R B-NHL cases could benefit from JWCAR029. R/R B-NHL cases administered JWCAR029 at 100×106 or 150×106 cells had a promising response rate, with durable PFS and sustained OS benefits after 12 months. The effectiveness and safety of JWCAR029 need to be confirmed in the real-world setting. Clinical trial information: NCT03344367.